rs2305498

Positions:

• chr11-69099446-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637342.1(TPCN2):​c.2003+13516G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,218 control chromosomes in the GnomAD database, including 3,421 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3421 hom., cov: 33)
• Consequence: TPCN2 ENST00000637342.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.950

Genes affected

TPCN2 (HGNC:20820): (two pore segment channel 2) This gene encodes a putative cation-selective ion channel with two repeats of a six-transmembrane-domain. The protein localizes to lysosomal membranes and enables nicotinic acid adenine dinucleotide phosphate (NAADP) -induced calcium ion release from lysosome-related stores. This ubiquitously expressed gene has elevated expression in liver and kidney. Two common nonsynonymous SNPs in this gene strongly associate with blond versus brown hair pigmentation.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPCN2	ENST00000637342.1	c.2003+13516G>A		intron_variant		5
TPCN2	ENST00000637504.1	c.*33+14160G>A		intron_variant		5
TPCN2	ENST00000635811.1	c.*867+11080G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31277 AN: 152100 Hom.: 3421 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.192

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.206 AC: 31294 AN: 152218 Hom.: 3421 Cov.: 33 AF XY: 0.216 AC XY: 16059 AN XY: 74416

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.197

Alfa AF: 0.202 Hom.: 1611

Bravo AF: 0.193

Asia WGS AF: 0.298 AC: 1033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.4
DANN	Benign	0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2305498; hg19: chr11-68866914;